[Psychiatric and psychological features of nicotine dependence].

Nicotine dependence involves both psychological and physiological dependence on nicotine. Evidences suggest that nicotine depends on dopamine for its reinforcing effects. A recent summary description of the clinical aspects of nicotine dependence disorders is provided in the DSM-IV-TR of the American Psychiatric Association. Nicotine withdrawal is defined by the DSM-IV-TR as a condition in which a person, after using nicotine daily for at least several weeks, exhibits at least four of the following symptoms within 24 hours after reduction or cessation of nicotine use: (1) dysphoric or depressed mood, (2) insomnia, (3) irritability, frustration or anger, (4) anxiety, (5) difficulty concentrating, (6) restlessness, (7) decreased heart rate, (8) increased appetite or weight gain. Among those symptoms, depression needs special consideration.

Efficacy and safety of a novel ĸ-agonist for managing intractable pruritus in dialysis patients.

BACKGROUND: Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year. METHODS: This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch. RESULTS: Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation. CONCLUSIONS: Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems.

[The definition of drug dependence].

A number of definitions of drug dependence exist. The current idea is summarized as follows: drug dependence is a chronic, progressive disease characterized by significant impairment that is directly associated with persistent and excessive use of a psychoactive substance. Impairment may involve physiological, psychological, or social dysfunction. The most helpful one to physicians is based on the descriptions of WHO's ICD and APA's DSM. The criteria for drug dependence of ICD-10 and DSM-IV are given in this paper. To facilitate the harmonization process of the forthcoming development of DSM V and ICD-11, differences in the both definitions are also discussed.

Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine.

The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.

Nicotine normalizes increased prefrontal cortical dopamine D1 receptor binding and decreased working memory performance produced by repeated pretreatment with MK-801: a PET study in conscious monkeys.

The effects of acute nicotine were determined on dopamine (DA) D(1) (D(1)R) and D(2) (D(2)R) receptor binding in the neocortex of conscious monkeys under control conditions as well as after chronic pretreatment with MK-801 (dizocilpine), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Extrastriatal neocortical D(1)R and D(2)R binding was evaluated with [(11)C]NNC112 and [(11)C]FLB457 with high-specific radioactivity using positron emission tomography (PET). Acute administration of nicotine bitartrate, given as an intravenous (i.v.) bolus plus infusion for 30 min at doses of 32 microg/kg+0.8 microg/kg/min or 100 microg/kg+2.53 microg/kg/min as base, induced slight but significant dose-dependent increases of DA in the extracellular fluid of prefrontal cortex (PFC) as determined by microdialysis. However, acute nicotine did not affect either [(11)C]NNC112 or [(11)C]FLB457 binding to D(1)R or D(2)R, respectively, in any cortical region. Chronic MK-801 (0.03 mg/kg, intramuscularly (i.m.), twice daily for 13 days) increased [(11)C]NNC112 binding to D(1)R in PFC. No significant changes were detected in [(11)C]FLB457 binding to PFC D(2)R. Although chronic MK-801 lowered baseline DA and glutamate levels in PFC, acute nicotine normalized reduced DA to control levels. Acute nicotine dose-dependently normalized the increased binding of [(11)C]NNC112 to D(1)R produced by chronic MK-801 but [(11)C]FLB457 binding to PFC D(2)R did not change. Working memory performance, impaired after chronic MK-801, was partially improved by acute nicotine. These results demonstrate that acute nicotine normalizes MK-801-induced PFC abnormality of D(1)R in PFC.

Clinical features of nicotine dependence compared with those of alcohol, methamphetamine, and inhalant dependence.

A new clinical evaluation form was developed to compare the clinical features of nicotine dependence with those associated with other abused drugs. A new scoring system for clinical evaluation was developed. The form consisted of five scoring items: subjective effects, liking (of drug), withdrawal syndrome, acute psychic and physical disorders, and social disturbance. A preliminary clinical investigation was performed to test the validity of the evaluation form. Study subjects were those showing dependence on nicotine (cigarette smoking, n = 40), alcohol (n = 39), methamphetamine (n = 31), and inhalants (n = 30), who fulfilled the DSM-IV-TR criteria for drug dependence disregarding the state of "a maladaptive pattern of substance use, leading to clinically significant impairment or distress," and gave written informed consent for participation in the study. Nicotine caused a mild or the least degree of subjective effects, liking, and psychic and physical withdrawal symptoms, without any significant social disturbance or acute disorders. With alcohol, liking, withdrawal syndrome, and acute physical disorders were prominent. Methamphetamine produced the most serious acute psychic disorders, with intensive acute physical disorders and psychic withdrawal symptoms. Inhalants were characterized by an intensive degree of acute psychic disorders. As for social disturbance, alcohol, methamphetamine, and inhalants showed more significant influence than nicotine. Our study findings revealed that the clinical features of drug dependence could be evaluated by using the new clinical evaluation form. Further study is required to clarify the clinical features of nicotine dependence compared with those of other drugs of dependence.

[Studies on clinical characteristics of nicotine dependence using a two compartment model of drug dependence].

The purpose of the present study was to develop a new clinical evaluation form to compare the clinical characteristics of nicotine dependence with those associated with other drugs of abuse, using a two-compartment model consisting of "drug dependence" and "dependence syndrome". The evaluation form consisted of five scoring items: subjective effects, drug liking, withdrawal syndrome, acute psychic and acute physical disorders, and social disturbance. "Drug dependence" was defined by positive scores on the "drug liking" item. "Dependence syndrome" was defined by positive scores on drug-induced pathological symptoms (withdrawal syndrome, and acute psychic and physical disorders) and social disturbance. The subjects were dependent on nicotine (cigarette smoking) (n = 114), alcohol (n = 101), methamphetamine (n = 90), inhalants (n = 63), and benzodiazepines (n = 39). All subjects met the DSM-IV-TR criteria for drug dependence. Nicotine produced a mild or the least degree of drug liking and withdrawal syndrome, without any significant social disturbance, or acute disorders. The other four drugs produced more intensive degrees of withdrawal syndrome and acute psychic and physical symptoms, with more significant social disturbance than nicotine. The present study indicated that nicotine dependence differed from other forms of drug dependence in that nicotine was not associated with "dependence syndrome".

Comparative effects of methamphetamine and nicotine on the striatal [(11)C]raclopride binding in unanesthetized monkeys.

Although a very large literature exists on the in vitro, ex vivo, and in vivo effects of nicotine on dopamine release in rodents, similar data in primates are scant. This study was initiated to compare methamphetamine to nicotine given i.v. to normal unanesthetized monkeys using positron emission tomography (PET) techniques. Release of dopamine in the striatum using [(11)C]raclopride was determined indirectly in four nicotine-naïve adult Macaca mulatta monkeys under conscious and isoflurane-anesthetized conditions using high-resolution PET. [(11)C]Raclopride was given i.v. as a bolus injection followed by continuous infusion with steady state over 30-45 min. Nicotine bitartrate was then given as a bolus plus infusion for 30 min in doses of 32 microg/kg + 0.8 microg/kg/min or 100 microg/kg + 2.53 microg/kg/min as base. The larger doses of nicotine caused significant cardiovascular effects; these doses did not displace [(11)C]raclopride binding in either dorsal or ventral striatum under the anesthetized conscious condition. In contrast, isoflurane-anesthesia induced a slight but significant dose-dependent reduction of [(11)C]raclopride binding by nicotine even at the same doses used in the anesthetized condition. Methamphetamine in bolus doses of 0.1, 0.3, and 1.0 mg/kg i.v. under conscious condition caused a significant displacement of [(11)C]raclopride and isoflurane-anesthesia facilitated the displacement induced by nicotine. These results indicate that nicotine, in high tobacco-smoking-related doses, does not release sufficient brain dopamine to displace [(11)C]raclopride in the striatum in the awake and fully conscious state, in contrast to small doses of methamphetamine.